The Proteomics and Bioinformatics core (PBC) will provide a powerful and integrated data collection and analysis platform for the pilot projects outlined in this P20 proposal. The specific experimental designs and most of the preliminary data relevant to the individual pilot projects are outlined in those sections. Here we describe the methods of biochemical fractionation, proteomics, bioinformatics and their integration to address the relevant goals of the pilot projects. Aim 1: Develop detailed experimental designs in terms of appropriate biochemical procedures, appropriate choice of proteomics technologies, and appropriate sample numbers based on specific study power for the proteomics studies of all pilot projects. Aim 2: Provide quantitative 2-D gel analysis to discern changes in tissue protein expression for Pilot Projects. Aim 3: Using the high-resolution mass spectrometry instruments of the Center coupled to the advanced bioinformatics and biostatistical pipelines for analysis provide quantitative label free protein expression analysis using a "shotgun" proteomics approach. Aim 4: Using advanced network and pathway tools, provide novel insights into patho-physiological changes in disease cohorts. Based on these data, use conventional biochemical and LC-MS based validation procedures along with novel protein antibody chips to confirm observed and predicted expression changes. Overall the PBC will be closely integrated with the projects through regular meetings and use of the Center's laboratory information management system, the MIMI.